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Thyroxine
Kinds of Thyroxine Terms modified by Thyroxine Selected AbstractsKinetics of Thyroxine (T4) and Triiodothyronine (T3) Transport in the Isolated Rat HeartEXPERIMENTAL PHYSIOLOGY, Issue 1 2001Mirko A. Rosic The dynamics and kinetics of thyroid hormone transport in the isolated rat heart were examined using the modified unidirectional paired tracer dilution method. The uptake of 125I-thyroxine (125I-T4) and 125I-triiodothyronine (125I-T3) from the extracellular space into heart cells was measured relative to the extracellular space marker 3H-mannitol. The thyroid hormone maximal uptake was 54.4% for 125I-T4 and 52.15% for 125I-T3. The thyroid hormone net uptake was 25.69% for 125I-T4 and 25.49% for 125I-T3. Backflux from the intracellular space was 53.17% for 125I-T4 and 61.59% for 125I-T3. In the presence of unlabelled thyroid hormones, 125I-T4 and 125I-T3 maximal uptakes were reduced from 10.1 to 59.74% and from 34.6 to 65.3%, respectively, depending on the concentration of the unlabelled hormone, suggesting a saturable mechanism of the thyroid hormone uptake by the heart cells, with Km(T4)= 105.46 ,M and the maximal rate of 125I-thyroid hormone flux from the extracellular space to heart cells (Vmax(T4)) = 177.84 nM min,1 for 125I-T4 uptake, and Km(T3)= 80.0 ,M and Vmax(T3)= 118.5 nM min,1 for 125I-T3 uptake. [source] Thyroid dysfunction , weight problems and the psyche: the patients' perspectiveJOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 4 2000B. O'Malley Objective To establish the extent to which individuals with thyroid dysfunction consider weight as a problem and the relevance of psychological factors. Design Cross-sectional study of individuals with thyroid dysfunction. Participants Members of the British Thyroid Foundation. Main outcome measures Two self-administered questionnaires, tailored for hypothyroid and hyperthyroid patients, respectively, and circulated to all members of the British Thyroid Foundation. These questionnaires specifically targeted views on weight and the experiencing of psychological symptoms. Results Twenty-five per cent of hypothyroid individuals regained normal body weight on adequate treatment with Thyroxine but 75% did not. Only 19% of subjects had received dietary advice from their doctor. Eighty-seven per cent of hypothyroid individuals felt depressed prediagnosis and 80% remained so on adequate treatment. Thirty-nine per cent felt weight was a contributing factor. Fifty-five per cent of thyrotoxic subjects reported a weight problem on or after treatment, 69% exceeding their pretoxic weight. Only 28% had received dietary advice from their doctor. Seventy-eight per cent of thyrotoxic individuals reported mood problems when the thyroid was over active and of these 77% improved with therapy. Twenty-three per cent did not. In excess of 60% of individuals had persistent symptoms after treatment. Thirty-four per cent of these blamed a weight problem. Conclusion Weight is a major concern to the majority of patients with thyroid dysfunction, sometimes contributing to significant mood disturbance. All patients with thyroid dysfunction, particularly if over weight, should receive dietary advice. This must emphasize that thyroid hormone manipulation does not always solve the problem. Furthermore, the associated psychological problems of thyroid disease do not always settle with treatment to euthyroidism and may require therapy in their own right. [source] Modeling of the 5,-Deiodination of Thyroxine by Iodothyronine Deiodinase: Chemical Corroboration of a Selenenyl Iodide Intermediate,ANGEWANDTE CHEMIE, Issue 3 2010Kei Goto Dr. Was macht eine gute Höhle aus? Ein molekularer Hohlraum ermöglichte die Stabilisierung eines Selenenyliodid(RSeI)-Intermediats, das bei der Abspaltung des 5,-Iodsubstituenten eines Thyroxinderivats mit einem Organoselenol entsteht (siehe Schema). Die für den Iodthyronin-Deiodinase-Katalysezyklus vorgeschlagenen chemischen Prozesse wurden experimentell bestätigt. [source] Connective tissue panniculitis in a child with vitiligo and Hashimoto's thyroiditisAUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 1 2006Basit Mirza SUMMARY A 9-year-old girl presented with a 6-month history of inflamed tender nodules in the pretibial area. These eventually healed leaving depressed areas of atrophy and loss of subcutaneous tissue. Histology showed a predominantly lymphocytic lobular panniculitis, consistent with connective tissue panniculitis. Investigations revealed an elevated thyroid stimulating hormone, elevated thyroid antiperoxidase antibody and a weakly positive antinuclear antibody (titre 1 in 40). She was commenced on hydroxychloroquine 300 mg daily, which resulted in resolution of the panniculitis. She developed focal vitiligo on the thighs. This gradually improved with 0.1% mometasone furoate ointment. The hydroxychloroquine dose was tapered to 200 mg daily after 12 months, then to 100 mg daily after 18 months therapy. Her thyroid autoantibody levels continued to rise and the hydroxychloroquine was increased again to 300 mg daily. She became borderline hypothyroid. Hashimoto's thyroiditis was diagnosed. Thyroxine was instituted with a resultant improvement in her thyroid blood tests. The lipoatrophy has not developed further during 2-year follow up. [source] Short-term resolution of psoriasis after total thyroidectomy for euthyroid multinodular goitreAUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 3 2002Johanna Kuchel SUMMARY A 36-year-old Chinese female with an 8-year history of chronic, generalized plaque psoriasis demonstrated a marked improvement of the disease after removal of an intercurrent euthyroid multinodular goitre. Thyroxine was commenced immediately postoperatively. No thyroid antibodies were detected and thyroid function and calcium levels remained within normal limits both pre- and postoperatively. Four weeks following surgery, narrow-band ultraviolet B (nbUVB) therapy was recommenced for recurrent psoriasis. The manifestations of psoriasis at this stage were less severe than before thyroidectomy and responded well to treatment, whereas before surgery the response to therapy had been poor. One year following total thyroidectomy, the patient received very effective psoriasis control with nbUVB therapy. The possible role of surgery and thyroid hormones in altering the pathogenesis of psoriasis in the acute setting is clearly of interest and warrants further research consideration. [source] Effects of in utero exposure to 2,2,,4,4,,5,5,-hexachlorobiphenyl (PCB 153) on somatic growth and endocrine status in rat offspringCONGENITAL ANOMALIES, Issue 4 2008Kenichi Kobayashi ABSTRACT Exposure to polychlorobiphenyl (PCB) mixtures at an early stage of development has been reported to affect endocrine glands; however, little is known about the precise toxicological properties of individual PCB. The present study was undertaken to determine whether prenatal exposure to 2,2,,4,4,,5,5,-hexachlorobiphenyl (PCB 153), a di- ortho -substituted non-coplanar congener, affects postnatal development in rat offspring. Pregnant Sprague-Dawley rats (Crj: CD (SD) IGS) were given PCB 153 (0, 16, or 64 mg/kg/day) orally from gestational day (GD) 10 through GD 16, and developmental parameters in the male and female offspring were examined. We found no dose-dependent changes in body weight, body length (nose,anus length), tail length, or the weights of kidneys, testes, ovaries and uterus in offspring at 1 or 3 weeks of age. Liver weights were increased in the PCB 153,treated groups, although we observed a significant difference only in males. Anogenital distance was unaffected in the PCB 153,treated groups. We observed a significant dose-dependent decrease in the plasma concentrations of thyroxine and tri-iodothyronine, whereas those of thyroid-stimulating hormone were not significantly changed. In addition, there were no dose-dependent changes in plasma concentrations of growth hormone and insulin-like growth factor-I in any dose group. These findings suggest that prenatal exposure to PCB 153 (GD 10,16, 16,64 mg/kg/day) may alter the thyroid status in rat offspring to some extent without affecting somatic growth or its related hormonal parameters. [source] CPU-86017 improves the compromised blood,brain barrier permeability mediated by impaired endothelial no system and oxidative stress caused by L -thyroxineDRUG DEVELOPMENT RESEARCH, Issue 3 2005Rong-Hui Du Abstract Impaired endothelial cell (EC) function leads to alterations in the permeability of the blood,brain barrier (BBB). There are two aspects of the transport through the BBB: from the blood to the brain (influx) and from the brain to the blood (efflux). An impaired EC model induced by L -thyroxine that compromises the influx and efflux properties of the BBB was used to assess responses to the intervention of CPU-86017 (an antioxidant and calcium channel blocker) and propranolol. CPU-86017 (t1/2=1.5 h) was also used as a target drug, leaving no traces in the brain and blood 24 h after administration. The permeability of the BBB was evaluated by using CPU-86017 after iv and icv injection and concentrations in the blood and brain being measured by high-performance liquid chromatography. The bidirectional permeability of CPU-86017 was impaired and associated with a reduced NO bioavailability assessed functionally by the vasoactivity in the model. Partial relief of NO bioavailability and oxidative stress induced by propranolol was consistent with a recovery of BBB efflux alone. Complete recovery in the efflux and influx of the BBB by CPU-86017 was a result of the complete restoration of NO bioavailability and reduction in oxidative stress. Normal BBB influx is dependent on an intact endothelial NO system, and efflux could be restored easily by partial improvement of NO bioavailability. CPU-86017 is thus more effective than propranolol in protecting the endothelium from damage produced by L -thyroxine through oxidative stress. Drug Dev. Res. 64:145,156, 2005. © 2005 Wiley-Liss, Inc. [source] Enantioselective determination of thyroxine enantiomers by ligand-exchange CE with UV absorbance and ICP-MS detectionELECTROPHORESIS, Issue 10 2009Jianzhen Kang Abstract A simple CE method has been developed for the separation and determination of thyroxine (T4) enantiomers in pharmaceutical formulations. The method was based on ligand-exchange mechanism using a Cu(II)/L -proline complex as chiral selector. The effects of different parameters affecting separation such as chiral selector concentration, organic additive, buffer pH and temperature were investigated. A baseline separation of the two enantiomers was obtained at a Cu(II)/L -proline ratio of 1:8 in a borate buffer (15,mmol/L, pH 9.6) containing 10%,v/v acetonitrile. Under the optimized conditions, precision linearity range and detection limits of the developed enantioselective CE method were evaluated and compared using two different detection systems: conventional UV detection at 226,nm and iodine (127I)specific detection ("chiral speciation") with ICP-MS. Both methodologies show adequate analytical performance characteristics with detection limits around 0.30,,g/mL for each enantiomer of T4. Finally, a levothroid pharmaceutical formulation sample was successfully analyzed using both developed methods CE-UV and CE-ICP-MS. [source] Ammonium perchlorate effects on thyroid function and growth in bobwhite quail chicksENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 4 2004F. M. ANNE Mcnabb Abstract Bobwhite quail chicks were used to investigate ammonium perchlorate (AP; NH4ClO4) effects on thyroid function and growth. Beginning at 3 to 4 d posthatch, we evaluated organismal thyroid status (circulating hormones), activation of the hypo-thalamic-pituitary-thyroid axis (thyroid wt) and thyroidal hormone content over a wide range of AP concentrations (50 ,g/L , 4,000 mg/L) in drinking water, for relatively short (2-week) and longer (8-week) exposures. Thyroidal thyroxine (T4) content, the most sensitive index of decreased thyroid function, decreased markedly in response to increasing perchlorate exposure. Thyroid weight and plasma T4 were less sensitive indicators and similar in their ability to detect thyroid changes. Growth measurements (body wt and skeletal growth) were very insensitive indices. Because thyroids contain large hormone stores, with low exposures or short time periods, these stores can be used to maintain circulating hormones, at least temporarily. Most depletion of thyroidal T4 occurred during the first two weeks of AP exposure. Subsequent decreases were at a slower rate presumably because thyrotropin stimulation of the thyroids at least partially compensated for some of the perchlorate effect. Additional studies of the interactions between AP concentration and exposure time are needed for understanding the complex nature of thyroid responses to perchlorate. [source] The effects of polychlorinated biphenyls (Aroclor 1242) on thyroxine, estradiol, molt, and plumage characteristics in the American kestrel (Falco sparverius)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2002Michael J. Quinn Jr. Abstract The purpose of this experiment was to determine the effects of Aroclor 1242, a mixture of polychlorinated biphenyls (PCBs), on plumage characteristics and molt in the American kestrel, Falco sparverius. Several characteristics of plumage, including color and molt schedule, are modulated by hormonal signals and hence may be modified by endocrine-active contaminants. If so, the functions of plumage (e.g., communication for mating or territorial defense) may be compromised by exposure to such compounds. Captive American kestrels were fed Aroclor 1242 at 0, 6.0, and 60.0 ppm (n = 6 males and 6 females per treatment) mixed in their normal diet. Concentrations of plasma estradiol and thyroxine were measured weekly from the beginning of treatment. Measured plumage characteristics included width of the black subterminal band on the tail, color (a composite index of hue and saturation), reflectance from 230 to 800 nm, pattern of feather loss and regrowth on the tail and wing, and timing of onset and duration of molt. Aroclor 1242 depressed plasma thyroxine. Plasma estradiol levels remained low due to the phase of the breeding cycle. Treatments did not disrupt the measured plumage characteristics. This may be due to timing or dose of exposure or to genetic factors. [source] Assessing the joint effects of chlorinated dioxins, some pesticides and polychlorinated biphenyls on thyroid hormone status in Japanese breast-fed infantsENVIRONMETRICS, Issue 2 2003Takashi Yanagawa Abstract Joint effects of dioxin related chemicals (DXNs), hexachlorocyclohexanes (HCHs), DDT, dieldrin, heptachlor-epoxide (HCE), chlordane and polychlorinated biphenyls (PCB) on the levels of triirodothyronine (T3), thyroxine (T4), thyroid stimulating hormones (TSH) and thyroid binding globulin (TBG) in the peripheral blood of 101 breast-fed infants are studied. The statistical issue involved is how to estimate the effects based on data from volunteer subjects with possible measurement errors. A chain independent graph is applied for modeling the associations among factors, and dicotomizations of selected factors are performed for estimating the effects. Use of nonparametric methods with careful consideration of over-adjustment is suggested. It is shown that the estimated odds ratios of DXNs,DDT, the first principal component of DXNs and DDT, relative to TSH are 3.02 (p -value=0.03) and 7.15 (p -value=0.02), respectively, when PCB is not adjusted and adjusted for, respectively. Copyright © 2003 John Wiley & Sons, Ltd. [source] The Evaluation of Thyroid Functions, Thyroid Antibodies, and Thyroid Volumes in Children with Epilepsy during Short-Term Administration of Oxcarbazepine and ValproateEPILEPSIA, Issue 11 2006Ali Cansu Summary:,Purpose: The aim of this study was to evaluate the effects of short-term oxcarbazepine (OXC) and valproate (VPA) monotherapy on thyroid functions in children. Methods: Fifty-five newly diagnosed epileptic children with normal thyroid functions (confirmed with the thyrotropin releasing hormone stimulation test) participated in this study. VPA treatment was started in 30 patients and OXC in 25 patients. Serum thyroxine (T4), free thyroxine (fT4), triiodothyronine (T3), free triiodothyronine (fT3), reverse T3 (rT3), thyroid peroxidase antibodies (TPO-ab), and urine iodine levels were evaluated at baseline and at the third and sixth months of therapy. Results: In the OXC group, serum T4, fT4, T3, fT3, and rT3 levels were found to be decreased at the third and sixth months, the differences were significant compared to the baseline values except for fT3 levels at the third month and fT4 and rT3 levels at the sixth month (p < 0.05). At the sixth month, serum T4 level dropped below the normal reference value in 8 (32%), fT4 in 5 (20%), T3 in 4 (16%), and fT3 in 3 (12%) patients. In the VPA group, mean T4, fT4, T3, fT3, and rT3 levels at 3 and 6 months remained similar compared to the baseline values (p > 0.05). Mean serum thyroid stimulating hormone levels increased significantly at the sixth month compared to the baseline values in the VPA group (p < 0.05) while it remained unchanged in the OXC group (p > 0.05). There was no effect of either drug on urinary iodine excretion and serum TPO-ab levels remained in normal ranges throughout the study. Conclusions: In this prospective study, it is documented that children under short-term OXC or VPA therapy showed altered thyroid functions similar to the changes observed after long-term treatment. Although, the clinical significance of these results need to be evaluated with future studies, this observation of altered thyroid functions points out that thyroid functions may need to be monitored closely in children receiving antiepileptic treatment, even in the short-time interval. [source] Thyroid Function in Girls with Epilepsy with Carbamazepine, Oxcarbazepine, or Valproate Monotherapy and after Withdrawal of MedicationEPILEPSIA, Issue 3 2004Leena K. Vainionpää Summary: Purpose: Antiepileptic drugs may affect the serum thyroid hormone concentrations. The aim of this study was to evaluate thyroid function in 78 girls taking carbamazepine (CBZ), oxcarbazepine (OXC), or valproate (VPA) monotherapy for epilepsy and after withdrawal of the treatment. Methods: Forty-one girls taking VPA, 19 taking CBZ, and 18 taking OXC for epilepsy, as well as 54 healthy age-matched controls, aged 8 to 18 years, participated in the study. All the girls were examined clinically, and their pubertal stage was assessed. Blood samples were obtained for thyroid hormone and antibody assays. These examinations were repeated after a mean follow-up of 5.8 years to assess thyroid function, and 64 (82%) of 78 patients and 42 (78%) of 54 controls agreed to participate in the second evaluation. Results: In the first evaluation, the mean serum thyroid hormone concentrations were lower in the girls taking CBZ [thyroxine (T4), 70.2; SD, 10.9 nM; and free thyroxine (FT4), 11.5; SD, 1.8 pM] or OXC (T4, 74.9; SD, 16.4 nM; and FT4, 11.3; SD, 1.8 pM) than in the control girls (T4, 96.6; SD, 15.1 nM, and FT4, 14.4; SD, 1.5 pM; p < 0.001, all comparisons). However, thyrotropin (TSH) concentrations were normal in the girls taking CBZ or OXC. Sixty-three% of the girls taking CBZ and 67% of the girls taking OXC had serum T4 and/or FT4 levels below the lower limit of the reference range. The VPA-treated girls with epilepsy had normal serum T4 and FT4 concentrations, but slightly increased TSH levels (3.3; SD, 1.5 mU/L; p < 0.01) compared with the control girls (2.5; SD, 1.0 mU/L). Normal serum hormone concentrations were restored in the patients who discontinued the medication. Conclusions: Both CBZ and OXC reduce serum thyroid hormone concentrations in girls with epilepsy. Conversely, VPA is associated with normal serum thyroid hormone and increased thyrotropin levels. However, our results suggest that the changes in serum thyroid hormone and thyrotropin levels are reversible after withdrawal of the medication. [source] Thyroid hormone responses to endurance exerciseEQUINE VETERINARY JOURNAL, Issue S36 2006E. A. GRAVES Summary Reasons for performing study: Limited information exists about changes in circulating thyroid hormone concentrations during prolonged endurance exercise in horses. Objective: To examine the effects of prolonged exercise on serum iodothyronine concentrations in horses performing endurance exercise of varying distances. Methods: Serum concentrations of iodothyronines were measured in horses before and after completion of 40, 56, 80 and 160 km endurance rides (Study 1); daily during a 5 day, 424 km endurance ride (Study 2); and before and for 72 h after completion of a treadmill exercise test simulating a 60 km endurance ride (Study 3). Results: In Study 1, 40 and 56 km of endurance exercise had little effect on serum iodothyronine concentrations with the exception of a 10% decrease (P<0.05) in free thyroxine (FT4) concentration after the 56 km ride. In contrast, total thyroxine (T4), total triiodothyronine (T3), FT4 and free triiodothyronine (FT3) concentrations all decreased (P<0.05) after successful completion of 80 and 160 km rides, with decreases ranging from 13,31% and 47,54% for distances of 80 and 160 km, respectively. Further, pre-ride T4 concentration was lower (P<0.05) and FT3 concentration was higher (P<0.05) in horses competing 160 km as compared to horses competing over shorter distances. In Study 2, serum concentrations of T4, T3 and reverse triiodothyronine (rT3) progressively decreased (P<0.05) over the course of the multi-day ride. In Study 3, the greatest decrease (P<0.05) in all iodothyronines was observed at 12 h of recovery, ranging from 25% for FT4 to 53% for FT3, but all thyroid hormone concentrations had returned to the pre-exercise values by 24 h of recovery. Conclusion: Endurance exercise results in transient decreases in serum iodothyronine concentrations. Potential relevance: These data are important to consider when thyroid gland function is assessed by measurement of serum iodothyronine concentrations in endurance horses. [source] Interference in thyroid-stimulating hormone determinationEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 8 2010Mauro Imperiali Eur J Clin Invest 2010; 40 (8): 756,758 Abstract Background, Thyroid-stimulating hormone (TSH) measurement plays a major role in the diagnosis of thyroid disorders. Despite the good quality of immunochemical tests measuring TSH levels, the presence of interfering substances can sometimes alter the TSH results. Design, We reported the case of a 79-year-old man affected by primary autoimmune hypothyroidism hospitalized for pneumonia. A TSH value > 100 mIU L -1 (reference: 0.44 mIU L -1) was found at admission. No signs and symptoms of hypothyroidism were found upon clinical examination and serum concentration of the free thyroxine (FT4) was normal. Results, Serum treatment in heterophile antibody blocking tubes did not change the TSH result in our assay, while normal levels were found in a different immunoassay method. An abnormal pattern was found in protein electrophoresis at admission, with IgG / j and IgM / k monoclonal bands proved in immunofixation. Interestingly, the disappearance of monoclonal bands was paralleled with a normalization of the TSH value. Conclusions, We suggest in this study that the TSH determination might be influenced by the presence of transient paraproteins. [source] Thyroid hormones determine developmental mode in sand dollars (Echinodermata: Echinoidea)EVOLUTION AND DEVELOPMENT, Issue 6 2004Andreas Heyland Summary Evolutionary transitions in larval nutritional mode have occurred on numerous occasions independently in many marine invertebrate phyla. Although the evolutionary transition from feeding to nonfeeding development has received considerable attention through both experimental and theoretical studies, mechanisms underlying the change in life history remain poorly understood. Facultative feeding larvae (larvae that can feed but will complete metamorphosis without food) presumably represent an intermediate developmental mode between obligate feeding and nonfeeding. Here we show that an obligatorily feeding larva can be transformed into a facultative feeding larva when exposed to the thyroid hormone thyroxine. We report that larvae of the subtropical sand dollar Leodia sexiesperforata (Echinodermata: Echinoidea) completed metamorphosis without exogenous food when treated with thyroxine, whereas the starved controls (no thyroxine added) did not. Leodia sexiesperforata juveniles from the thyroxine treatment were viable after metamorphosis but were significantly smaller and contained less energy than sibling juveniles reared with exogenous food. In a second starvation experiment, using an L. sexiesperforata female whose eggs were substantially larger than in the first experiment (202±5 vs. 187±5 ,m), a small percentage of starved L. sexiesperforata larvae completed metamorphosis in the absence of food. Still, thyroxine-treated larvae in this experiment completed metamorphosis faster and in much higher numbers than in the starved controls. Furthermore, starved larvae of the sand dollar Mellita tenuis, which developed from much smaller eggs (100±2 ,m), did not complete metamorphosis either with or without excess thyroxine. Based on these data, and from recent experiments with other echinoids, we hypothesize that thyroxine plays a major role in echinoderm metamorphosis and the evolution of life history transitions in this group. We discuss our results in the context of current life history models for marine invertebrates, emphasizing the role of egg size, juvenile size, and endogenous hormone production for the evolution of nonfeeding larval development. [source] Thyroid hormone resistance: the role of mutational analysisINTERNAL MEDICINE JOURNAL, Issue 11 2006C. M. Florkowski Abstract The finding of increased thyroxine (T4) and tri-iodothyronine (T3) levels in a patient with normal or increased thyroid-stimulating hormone is unexpected and presents a differential diagnosis between a thyroid-stimulating hormone-secreting pituitary adenoma, generalized resistance to thyroid hormone (RTH) and laboratory artefact. Without careful clinical and biochemical evaluation, errors may occur in patient diagnosis and treatment. In the case of RTH, mutation of the thyroid hormone receptor beta gene results in generalized tissue resistance to thyroid hormone. As the pituitary gland shares in this tissue resistance, euthyroidism with a normal thyroid-stimulating hormone is usually maintained by increased thyroid hormones. To date, we have identified eight pedigrees in New Zealand with mutations in the thyroid hormone receptor beta gene, including two novel mutations. Mutational analysis of the thyroid hormone receptor beta gene allows definitive diagnosis of RTH, potentially avoiding the need for protracted and expensive pituitary function testing and imaging. Mutational analysis also enables family screening and may help to avoid potential misdiagnosis and inappropriate treatment. [source] Evidence for the presence of 5,-deiodinase in mammalian seminal plasma and for the increase in enzyme activity in the prepubertal testisINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 4 2000Brzezi, lebodzi Thyroid hormones are critical for structural and functional development of the testis and Sertoli cells are considered true target cells for triiodothyronine (T3). However, the role of thyroid hormones in the adult testis seems to be minimal and the mechanism by which they affect testicular function is not known. Due to the existing blood,testis barrier the concentration of thyroid hormones in seminal plasma is kept lower than in blood plasma. We have found that T3 may reach the testis not only from the circulation but also from local enzymic conversion of thyroxine to T3. The presence of the enzymic activity responsible for thyroxine 5,deiodination and for generating T3 locally was also found in boar's seminal plasma. The seminal plasma 5,-deiodinase (5,-D) appeared to be predominantly the propylthiouracil (PTU)-insensitive type II isoenzyme found, so far, in tissues where it plays a role in paracrine signalling. It contains selenocysteine in its molecule (inhibition by aurothioglucose), and has an apparent Km for reverse-T3 as substrate of 0.36 n M and a Vmax 23.8 fmol I,/mg protein/min. Because the seminal plasma 5,-D is partially, but uncompetitively, inhibited by PTU, the presence in seminal plasma of two 5,-D isoenzymes (type I and II) cannot be excluded. The 5,-D activity in testes increased significantly between week 3 and 4, and this increase was concomitant with increase in testicular size. The relationship between testicular weight gain and age showed a similar characteristic change and corresponded to the change in 5,-D activity. Unlike in rodents, the testis of the prepubertal pig has thyroid hormone receptors in Sertoli cells, and suggests that in growing piglets, testicular 5,-D is a key factor regulating local supply of biologically active T3, and is an essential factor in testicular paracrine function. The present results are the first demonstration and characterization of the 5,-deiodinase in seminal plasma. [source] Relationships of serum free thyroxine and erythrocyte measures in euthyroid HFE C282Y homozygotes and control subjects: the HEIRS StudyINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 3 2010J. C. BARTON Summary Hemoglobin (Hb) levels and mean corpuscular volume (MCV) are abnormal in some persons with hemochromatosis or thyroid disorders. We sought to determine whether serum free thyroxine (T4) affects erythrocyte measures in euthyroid adults with or without C282Y homozygosity. We evaluated 488 white HFE C282Y homozygotes and controls (no HFE C282Y or H63D; normal serum iron measures) identified in screening; we excluded those with thyroid disorders, anemia, erythrocytosis, or serum ferritin (SF) <34 pmol/l. In the remaining 141 C282Y homozygotes and 243 controls, we evaluated correlations of log10 free T4 with Hb, RBC, MCV, and red blood cell distribution width (RDW). C282Y homozygotes had lower mean age, higher mean Hb, MCV, and log10 SF, and lower mean RBC and RDW than controls; mean log10 free T4 did not differ significantly. In HFE C282Y homozygotes, there was no significant correlation of log10 T4 with erythrocyte measures. In controls, there was a positive correlation of log10 T4 with Hb (P = 0.0096) and a negative correlation with RDW (P = 0.0286). Among euthyroid white adults without iron deficiency, there are significant correlations of log10 free T4 with Hb and RDW in controls, but not in HFE C282Y homozygotes. [source] Effect of ovariectomy and ad libitum feeding on body composition, thyroid status, ghrelin and leptin plasma concentrations in female dogs,JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 1-2 2006I. Jeusette Summary The objective of this study was to evaluate the effects of ovariectomy (i) and ad libitum feeding (ii) on energy intake, body weight (BW), body composition, thyroid status, leptin and ghrelin plasma concentrations. Four young adult female Beagle dogs were fed a maintenance diet for 6 weeks prior to ovariectomy, then 6 months after. Food allowance was adjusted in order to maintain optimal BW. Then, a diet slightly higher in energy concentration was fed ad libitum for 4 months. The maintenance diet was then fed ad libitum for one additional month. The maintenance of optimal BW after ovariectomy required a significant decrease in energy allowance. No increase in fat mass was observed. Ghrelin concentration remained unchanged. During the first month of ad libitum feeding, plasma ghrelin concentration and energy intake increased, then they decreased. Mean BW, plasma leptin, thyrotropin (TSH), total triiodothyronine (TT3) and total thyroxine (TT4) concentrations significantly increased over the study. The BW increase was exclusively due to an increase in body fat. In conclusion, energy allowance should be strictly controlled in spayed female dogs. The results suggest that in dogs, thyroid hormones, leptin and ghrelin concentrations change in response to a positive energy balance in an attempt to limit weight gain. However, the significant weight gain shows that this goal was not achieved. [source] Goitrogenic activity of p -coumaric acid in ratsJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 6 2003Fatima Khelifi-Touhami Abstract The effects of three natural phenolic acids (caffeic, ferulic, and p -coumaric) on the rat thyroid gland were examined in a 3-week oral-treatment study. Forty male Wistar albino rats, divided into groups of 10 rats each and fed iodine-rich diet, were administered by gastrointestinal tube saline (control), caffeic acid, ferulic acid, or p -coumaric acid at a dose level of 0.25 ,mol/kg/day for 3 weeks. The mean absolute and relative thyroid weights in caffeic, ferulic, or p -coumaric acid groups were significantly increased to 127 and 132%, 146 and 153%, or 189 and 201% compared to control value, respectively. Histological examination of the thyroids of p -coumaric acid group revealed marked hypertrophy and/or hyperplasia of the follicles. Caffeic or ferulic groups showed slight to moderate thyroid gland enlargement. Thyroid lesions in p -coumaric acid group were associated with significant increases in cellular proliferation as indicated by [3H]thymidine incorporation. In addition, the goitrogenic effect of p -coumaric acid was further confirmed by significant decreases (50%) in serum tri-iodothyronine (T3) and thyroxine (T4), and a parallel increase (90%) in serum thyroid stimulating hormone (TSH) compared to control group. These results indicate that administration of p -coumaric acid at relatively high doses induces goiter in rats. © 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:324,328, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10094 [source] The role of thyroid hormone on phenylhydrazine hydrochloride mediated inhibitory effects on blood acetylcholinesterase: An in vivo and in vitro studyJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 4 2002Mitali Banerjee Abstract A novel phenomenon of protective counteraction by thyroid hormone has been demonstrated in phenylhydrazine hydrochloride (PHH) induced insult on blood acetylcholinesterase (AChE, EC 3.1.1.7) activity, in both, in vivo and in vitro conditions. Injection of PHH (20 ,g/g) to juvenile male rats for three consecutive days caused a 48% decrease (p < 0.001) in the total blood AChE activity on the third day (i.e. 24 h after injections for three consecutive days) in comparison to the control animals. Simultaneous injections of thyroxine (T4) 1 or 2 ,g/g with PHH (20 ,g/g) showed a recovery in AChE activity by 27% (p < 0.02) and 55% (p < 0.001), respectively, in comparison to the only PHH-injected animals. T4 at 1, 2 and 4 ,g/g doses showed unchanged levels in comparison to the untreated controls. In our in vitro system, incubations of the RBCs in PHH (2 mM) containing medium also showed an inhibition of 44% (p < 0.001) of the RBC membrane AChE activity in comparison to the control conditions. A recovery of 23,81% of the enzyme activity was observed after simultaneous use of T4 (1 nM,100 nM) or T3 (0.1 nM,100 nM), or triiodothyroacetic acid (TRIAC) (100 nM) with PHH (2 mM) in a dose-dependent manner with a potency profile of T3 > T4 > TRIAC. Incubation of RBCs only with T4, T3, or TRIAC at 0.1,100 nM concentration did not cause any alteration in the membrane AChE activity in comparison to control conditions. Thus, thyroid hormone distinctly demonstrated a counteraction or protective nature of action on the PHH-induced inhibition of total blood and RBC membrane AChE activity. © 2002 Wiley Periodicals, Inc. J Biochem Mol Toxicol 16:162,168, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10039 [source] Thyroid-Stimulating Hormone Restores Bone Volume, Microarchitecture, and Strength in Aged Ovariectomized Rats*,,§JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2007T Kuber Sampath PhD Abstract We show the systemic administration of low levels of TSH increases bone volume and improves bone microarchitecture and strength in aged OVX rats. TSH's actions are mediated by its inhibitory effects on RANKL-induced osteoclast formation and bone resorption coupled with stimulatory effects on osteoblast differentiation and bone formation, suggesting TSH directly affects bone remodeling in vivo. Introduction: Thyroid-stimulating hormone (TSH) receptor haploinsufficient mice with normal circulating thyroid hormone levels have reduced bone mass, suggesting that TSH directly affects bone remodeling. We examined whether systemic TSH administration restored bone volume in aged ovariectomized (OVX) rats and influenced osteoclast formation and osteoblast differentiation in vitro. Materials and Methods: Sprague-Dawley rats were OVX at 6 months, and TSH therapy was started immediately after surgery (prevention mode; n = 80) or 7 mo later (restoration mode; n = 152). Hind limbs and lumbar spine BMD was measured at 2- or 4-wk intervals in vivo and ex vivo on termination at 8,16 wk. Long bones were subjected to ,CT, histomorphometric, and biomechanical analyses. The direct effect of TSH was examined in osteoclast and osteoblast progenitor cultures and established rat osteosarcoma-derived osteoblastic cells. Data were analyzed by ANOVA Dunnett test. Results: In the prevention mode, low doses (0.1 and 0.3 ,g) of native rat TSH prevented the progressive bone loss, and importantly, did not increase serum triiodothyroxine (T3) and thyroxine (T4) levels in aged OVX rats. In restoration mode, animals receiving 0.1 and 0.3 ,g TSH had increased BMD (10,11%), trabecular bone volume (100,130%), trabecular number (25,40%), trabecular thickness (45,60%), cortical thickness (5,16%), mineral apposition and bone formation rate (200,300%), and enhanced mechanical strength of the femur (51,60%) compared with control OVX rats. In vitro studies suggest that TSH's action is mediated by its inhibitory effects on RANKL-induced osteoclast formation, as shown in hematopoietic stem cells cultivated from TSH-treated OVX rats. TSH also stimulates osteoblast differentiation, as shown by effects on alkaline phosphatase activity, osteocalcin expression, and mineralization rate. Conclusions: These results show for the first time that systemically administered TSH prevents bone loss and restores bone mass in aged OVX rats through both antiresorptive and anabolic effects on bone remodeling. [source] Thyroid Hormones Promote Chondrocyte Differentiation in Mouse ATDC5 Cells and Stimulate Endochondral Ossification in Fetal Mouse Tibias Through Iodothyronine Deiodinases in the Growth Plate,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2002Masako Miura Abstract Thyroid hormones (THs), 3,3,,5-triiodo- L -thyronine (T3) and L -thyroxine (T4), are important for the normal development of the growth plate (GP); congenital TH deficiency leads to severe dwarfism. In mouse chondrogenic cell line, ATDC5, T3 enhanced differentiation and increased Alizarin red staining, but did not affect Alcian blue staining. In organ-cultured mouse tibias, THs stimulated the cartilage growth, especially in the hypertrophic zone. Interestingly, T4 was as equally potent as T3 in organ-cultured tibias, which suggests that T4 is metabolized locally to T3, because T4 is a prohormone and must be converted to T3 for its activity. Two enzymes catalyze the conversion; type I deiodinase (D1) and type II deiodinase (D2). D1 has a ubiquitous distribution and D2, with a high affinity for T4, is present where the maintenance of intracellular T3 concentration is critical. Messenger RNAs (mRNAs) for D1 and D2 were detected in neonatal mouse tibias and ATDC5 cells. The enzyme activity was unaffected by the D1 inhibitor 6-propyl-2-thiouracil, suggesting that D2 mainly catalyzes the reaction. D2 mRNA was detected in differentiated ATDC5 cells. In organ-cultured mouse tibias, D2 activity was greater at later stages. In contrast, thyroid hormone receptors (TRs) were expressed in neonatal mouse tibias and ATDC5 cells, but their expression levels in ATDC5 cells were stable throughout the culture periods. Therefore, increased T3 production at later stages by D2 is likely to contribute to the preferential effects of THs in the terminal differentiation of GP. This article is the first to show that T4 is activated locally in GP and enhances the understanding of TH effects in GP. [source] Does diagnostic sonography alter thyroid and parathyroid hormone levels?JOURNAL OF CLINICAL ULTRASOUND, Issue 1 2008Erdinc Serin MD Abstract Purpose To investigate possible alterations in the levels of thyroid and parathyroid hormones (PTHs) and thyroglobulin (TG) in healthy individuals following diagnostic sonographic examination of the thyroid gland. Methods Thirty healthy women with no pathologic findings underwent sonographic examination, followed 6 weeks later by a second examination involving a probe-only application (PA) with the ultrasound scanner switched off. Duration times were identical for both examinations. Blood was drawn before and after the 2 applications. Thyroid hormone, PTH, and TG levels before and after the 2 applications were compared, and the difference between the variations for each parameter in the first and second applications was assessed. Blood samples were taken before and after the sonographic examination and the PA, and the serum concentrations of sensitive thyrotropin, total and free thyroxine, total and free tri-iodothyronine, TG, and PTH were measured. The pre- and post-examination levels of the hormones for the 2 applications were then compared and the difference between the variations for each parameter in the first and second application was then assessed. Results The only significant variations observed were in the TG levels after PA and PTH levels after both sonographic examination and PA. The comparison between the 2 difference values revealed no significant difference except for PTH. Conclusion This preliminary report on the possible influence of sonographic examination of the thyroid on the serum levels of thyroid and parathyroid hormones suggests that gland secretions such as PTH may be affected by external factors, including ultrasound. Clinicians should be aware of alterations in hormone levels by external factors. © 2007 Wiley Periodicals, Inc. J Clin Ultrasound, 2008 [source] Methimazole protects lungs during hepatic ischemia,reperfusion injury in rats: An effect not induced by hypothyroidismJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 5 2007Tanju Tütüncü Abstract Background:, Hepatic ischemia,reperfusion injury may lead to remote organ failure with mortal respiratory dysfunction. The aim of the present study was to analyze the possible protective effects of methimazole on lungs after hepatic ischemia,reperfusion injury. Methods:, Forty male Wistar albino rats were randomized into five groups: a control group, in which bilateral pulmonary lobectomy was done; a hepatic ischemia,reperfusion group, in which bilateral pulmonary lobectomy was done after hepatic ischemia,reperfusion; a thyroidectomy,ischemia,reperfusion group (total thyroidectomy followed by, 7 days later, bilateral pulmonary lobectomy after hepatic ischemia,reperfusion); a methimazole,ischemia,reperfusion group (following methimazole administration for 7 days, bilateral pulmonary lobectomy was done after hepatic ischemia,reperfusion); and a methimazole +l -thyroxine,ischemia,reperfusion group (following methimazole and l -thyroxine administration for 7 days, bilateral pulmonary lobectomy was performed after hepatic ischemia,reperfusion). Pulmonary tissue specimens were evaluated histopathologically and for myeloperoxidase and malondialdehyde levels. Results:, All of the ischemia,reperfusion intervention groups had higher pulmonary injury scoring indices than the control group (P < 0.001). Pulmonary injury index of the ischemia,reperfusion group was higher than that of both the methimazole-supplemented hypothyroid and euthyroid groups (P = 0028; P = 0,038, respectively) and was similar to that of the thyroidectomized group. Pulmonary tissue myeloperoxidase and malondialdehyde levels in the ischemia,reperfusion group were similar with that in the thyroidectomized rats but were significantly higher than that in the control, and both the methimazole-supplemented hypothyroid and euthyroid groups. Conclusion:, Methimazole exerts a protective role on lungs during hepatic ischemia,reperfusion injury, which can be attributed to its anti-inflammatory and anti-oxidant effects rather than hypothyroidism alone. [source] Gastric emptying function changes in patients with thyroid cancer after withdrawal of thyroid hormone therapyJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 6 2004PAN-FU KAO Abstract Background:, Hypothyroidism is commonly thought to cause decreased gastric emptying but is mostly associated with autoimmune disease. In the present study the gastric emptying function of thyroid cancer patients with severe hypothyroidism of short duration was evaluated with a radionuclide solid meal gastric emptying study. Methods:, Twenty-two patients who had undergone surgical operation and 131I ablation for thyroid cancer participated in solid meal gastric emptying studies before the withdrawal of thyroxine and then again 4 weeks after the withdrawal of thyroxine. Eleven patients had an additional gastric emptying study at 6 weeks after withdrawal of thyroxine. Gastric emptying curves and emptying parameters were calculated. Student's paired t -test was used for statistical analysis of data for all cases between the baseline and at 4 weeks after withdrawal. An additional repeated measure anova with multiple comparisons was performed on data between baseline, 4 weeks and 6 weeks after withdrawal for the other 11 patients. All P values presented are two-tailed and the significance level is 0.05. Results:, Hypothyroidism status was confirmed by the marked change of the serum thyroxine and thyroid-stimulating hormone 4 weeks and 6 weeks after withdrawal of the thyroxine replacement (P < 0.001). The gastric half-emptying time and emptying rate changed significantly after short-term severe thyroid hormone deficiency (P < 0.005). However, the length of the lag phase did not have a statistically significant change at 4 weeks or 6 weeks after withdrawal of the thyroxin replacement (P = 0.219 and 0.142). Conclusions:, Hypothyroidism following the withdrawal of the thyroxine replacement in thyroid cancer patients preparing for 131I cancer work-up can significantly prolong gastric half-emptying time and emptying rate. [source] Altered Thyroid Hormones and Behavioural Change in a Sub-Population of Rats Following Chronic Constriction InjuryJOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2010E. Kilburn-Watt Hypothyroidism is associated with a disturbance of behaviour and mood. There are also individuals, not classified as hypothyroid, with low to ,low normal' thyroid hormone levels and normal thyroid-stimulating hormone (TSH) levels who have mood and behavioural changes. As the peripheral thyroid hormones decrease, TSH is expected to increase. However, there are a number of physiological mechanisms known to suppress TSH. In the present study, we report on thyroid hormone regulation in a rat model of neuropathic pain and altered social behaviour that is usually transient, but is persistent in a sub-group of the population. Following ligation of the sciatic nerve, male Sprague-Dawley rats were assessed for social dominance towards an intruder: 20% showed persistently decreased social dominance. Plasma levels of thyroid hormones, TSH and corticosterone were measured before and on days 2, 3, 4, 5 and 6 after injury in 21 rats. The mean plasma thyroxine (T4), free thyroxine (fT4) and triiodothyronine (T3) levels decreased significantly post-injury in rats with persistently changed behaviour compared to rats with unchanged behaviour (P , 0.002). There was no significant difference between groups for mean change in free triiodothyronine (fT3) or TSH. There was a correlation between decreased dominance behaviour and decrease in both T4 (r = 0.62, P = 0.009) and fT4 (r = 0.71, P = 0.001), but no correlation with TSH. In a sub-population of rats, decreased thyroid hormones did not result in the expected increased levels of TSH to restore pre-injury levels, nor did they show increased hypothalamic thyrotrophin-releasing hormone mRNA expression, indicating altered hypothalamic-pituitary-thyroid axis regulation. Because T3 availability to the brain is dependent on both circulating T3 and T4, decreased peripheral thyroid hormones may result in changed neural function, as expressed in altered complex behaviours in this sub-population of rats. [source] Thyroid Hormone Action: Nongenomic Modulation of Neuronal Excitability in the HippocampusJOURNAL OF NEUROENDOCRINOLOGY, Issue 2 2009M. A. Caria Years of effort have failed to establish a generally-accepted mechanism of thyroid hormone (TH) action in the mature brain. Recently, both morphological and pharmacological evidence have supported a direct neuroactive role for the hormone and its triiodinated metabolites. However, no direct physiological validation has been available. We now describe electrophysiological studies in vivo in which we observed that local thyroxine (T4) administration promptly inhibited field excitatory postsynaptic potentials recorded in the dentate gyrus (DG) with stimulation of the medial perforant pathway, a result that was found to be especially pronounced in hypothyroid rats. In separate in vitro experiments, we observed more subtle but statistically significant responses of hippocampal slices to treatment with the hormone. The results demonstrate that baseline firing rates of CA1 pyramidal cells were modestly reduced by pulse-perfusion with T4. By contrast, administration of triiodothyronine (T3) was often noted to have modest enhancing effects on CA1 cell firing rates in hippocampal slices from euthyroid animals. Moreover, and more reliably, robust firing rate increases induced by norepinephrine were amplified when preceded by treatment with T3, whereas they were diminished by pretreatment with T4. These studies provide the first direct evidence for functional, nongenomic actions of TH leading to rapid changes in neuronal excitability in adult rat DG studied in vivo and highlight the opposing effects of T4 and T3 on norepinephrine-induced responses of CA1 cells studied in vitro. [source] Thyroxine Modulates Corticotropin-Releasing Factor but not Arginine Vasopressin Gene Expression in the Hypothalamic Paraventricular Nucleus of the Developing RatJOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2000N. Dakine Neonatal rats were daily injected with 100 ,g/kg T4 and killed at 4, 8 or 15 days. Circulating corticosterone and corticosteroid binding globulin concentrations increased in 8- and 15-day-old rats after T4 treatment. Plasma adrenocorticotropic hormone (ACTH) concentrations, pituitary ACTH content and pro-opiomelanocortin mRNA expression were unaffected in T4 -treated rats. T4 treatment induced an increase in corticotropin-releasing factor (CRF) mRNA expression in the whole population of CRF synthesizing cells of the paraventricular nucleus (PVN) that became significant at day 8 and disappeared at day 15. Double labelling in situ hybridization revealed that CRF gene expression in the CRF+/arginine vasopressin (AVP)+ subpopulation was increased at days 4 and 8 and decreased at day 15. CRF immunoreactivity in the zona externa of the median eminence increased with age but was not affected by the experimental hyperthyroidism. The degree of CRF and AVP colocalization, the concentration of AVP mRNA in the parvo and magnocellular cell bodies of the PVN and the density of immunoreactive AVP in the zona interna or zona externa of the median eminence did not change after T4 treatment. Our data demonstrate that experimental hyperthyroidism accelerates the maturation of hypothalamic CRF gene expression, including in particular in the CRF+/AVP+ subpopulation, during the stress hyporesponsive period. These observations suggest that the physiological peak of plasma thyroxine that occurs between days 8,12 may participate in the maturation of hypothalamic CRF cells. [source] | |||||||||||||||||||||||||||||||||||||||||||